title: Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial.
abstract: OBJECTIVE
  Open-label, phase III trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer.
  
  
  METHODS
  Patients were stratified and randomly assigned to receive sunitinib 37.5 mg once per day or sorafenib 400 mg twice per day. Primary end point was overall survival (OS).
  
  
  RESULTS
  Early trial termination occurred for futility and safety reasons. A total of 1,074 patients were randomly assigned to the study (sunitinib arm, n = 530; sorafenib arm, n = 544). For sunitinib and sorafenib, respectively, median OS was 7.9 versus 10.2 months (hazard ratio [HR], 1.30; one-sided P = .9990; two-sided P = .0014); median progression-free survival (PFS; 3.6 v 3.0 months; HR, 1.13; one-sided P = .8785; two-sided P = .2286) and time to progression (TTP; 4.1 v 3.8 months; HR, 1.13; one-sided P = .8312; two-sided P = .3082) were comparable. Median OS was similar among Asian (7.7 v 8.8 months; HR, 1.21; one-sided P = .9829) and hepatitis B-infected patients (7.6 v 8.0 months; HR, 1.10; one-sided P = .8286), but was shorter with sunitinib in hepatitis C-infected patients (9.2 v 17.6 months; HR, 1.52; one-sided P = .9835). Sunitinib was associated with more frequent and severe adverse events (AEs) than sorafenib. Common grade 3/4 AEs were thrombocytopenia (29.7%) and neutropenia (25.7%) for sunitinib; hand-foot syndrome (21.2%) for sorafenib. Discontinuations owing to AEs were similar (sunitinib, 13.3%; sorafenib, 12.7%).
  
  
  CONCLUSIONS
  OS with sunitinib was not superior or equivalent but was significantly inferior to sorafenib. OS was comparable in Asian and hepatitis B-infected patients. OS was superior in hepatitis C-infected patients who received sorafenib. Sunitinib-treated patients reported more frequent and severe toxicity.
authors.affiliation: Ann-Lii Cheng, National Taiwan University Hospital, Taipei; Deng-Yn Lin, Chang Gung Memorial Hospital, Chang Gung University, Guishan Township, Taiwan, Republic of China; Yoon-Koo Kang, Asan Medical Center, University of Ulsan College of Medicine; Hyun-Cheol Chung, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul; Joong-Won Park, National Cancer Center, Goyang, Republic of Korea; Masatoshi Kudo, Kinki University Hospital, Osaka; Masao Omata, Yamanashi Prefecture Central Hospital, Kofu, Yamanashi, Japan; Shukui Qin, Nanjing Bayi Hospital, Nanjing; Xiangqun Song, Tumor Hospital of Guangxi Zhuang Autonomous Region, Nanning; Jianming Xu, Beijing 307 Hospital Cancer Centre, Beijing, People's Republic of China; Guido Poggi, Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Maugeri, Pavia; Silvana Lanzalone, Maria Jose Lechuga, Pfizer Italia Srl, Milan, Italy; Susan Pitman Lowenthal, Pfizer Oncology, New York, NY; Liqiang Yang, Pfizer Oncology, La Jolla, CA; Eric Raymond, Service Inter Hospitalier de Cancerologie Bichat-Beaujon, Clichy, France.
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.forename: Yoon-Koo
authors.initials: YK
authors.lastname: Kang
authors.forename: Deng-Yn
authors.initials: DY
authors.lastname: Lin
authors.forename: Joong-Won
authors.initials: JW
authors.lastname: Park
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
authors.forename: Shukui
authors.initials: S
authors.lastname: Qin
authors.forename: Hyun-Cheol
authors.initials: HC
authors.lastname: Chung
authors.forename: Xiangqun
authors.initials: X
authors.lastname: Song
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
authors.forename: Guido
authors.initials: G
authors.lastname: Poggi
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
authors.forename: Susan
authors.initials: S
authors.lastname: Pitman Lowenthal
authors.forename: Silvana
authors.initials: S
authors.lastname: Lanzalone
authors.forename: Liqiang
authors.initials: L
authors.lastname: Yang
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Lechuga
authors.forename: Eric
authors.initials: E
authors.lastname: Raymond
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000627:therapeutic use*; D000077157:Sorafenib; D000077210:Sunitinib; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib